Many DERC investigators share a common need for high-speed fluorescence imaging of cells in both 2 and 3 dimensions. The instrumentation and software developments of the Biomedical Imaging Group are largely determined by the evolving needs of these studies. The work is performed on unique instruments and analysis software developed by the faculty of the Biomedical Imaging Group (BIG), in whose laboratory the core is located, and is highly collaborative in nature. The central instrumentation of the Cell Imaging Core are: 1) a high-resolution, Fluorescence Digital Imaging Microscope (F-DIM) for 2-D imaging and 3-D reconstruction of molecular distributions inside fixed and living cells;2) a unique, custom-built high-speed F-DIM for 2-D imaging of very rapid molecular dynamics (e.g. local calcium signaling) and fast (<1 sec.) 3-D imaging of molecular distributions in living cells;3) a new Total Internal Reflection Fluorescence (TIRF) microscope for high-speed imaging of near membrane molecules;4) a new Multi-photon fluorescence microscope with the ability to image deep into living tissue. In addition, the Imaging Core provides high-speed computational facilities, numerous 3-D graphical workstations with custom software for image processing, visualization and analysis, and for computer simulation of molecular interactions inside cells. Strong, grant-funded (NIH R01, PPG) collaborations with DERC members Czech, Corvera, and Ikebe have provided driving biological problems, and the ability to commit our resources to the development of complex instrumentation and software systems in the BIG laboratory. Funding from the DERC Imaging Core has enabled us to develop further and to refine these advances in instrumentation, and to offer assistance, training, and access to more DERC members (Davis, Doxsey, Rock, Bortell, Greiner, Mordes, Rossini, Mello). Support from the DERC has allowed us to commit to expanding (e.g. multi-photon microscopy) with a focus on future DERC utilization and collaborations. We were able recruit and hire an Optical Physicist (C. Standley) with expertise in optics, imaging, lasers, and image processing, to work on TIRF and multi-photon microscopy, two of the newest instruments available in BIG and to the DERC members.